The incidence and prevalence of gout and hyperuricemia (the metabolic underpinning of gout) have been increasing steadily over the past 40 years. From the mid-1960s to the mid-1990s, the prevalence of gout increased in most westernized countries two- to threefold, and it is now the most common inflammatory arthritis in men.1
Recent explorations of this epidemic focus on:
- The rise in obesity and the metabolic syndrome (of which hyperuricemia is a feature)2
- The aging of the population and age-related decline in renal clearance (and, in turn, the clearance of uric acid)3
- The increasing prevalence of hypertension and frank renal disease4
- The widespread use of thiazide diuretics, which elevate uric acid5
- A rising consumption of beer and foods high in purines (leading to elevated levels of urate)6
- A dietary trend toward consuming fructose-based drinks and fructose-flavored foods (which elevate uric acid).7
In spite of the increase in clinical cases, gout remains very poorly managed. Practitioners often miss the diagnosis, confuse the treatment of acute and chronic gout, and fail to correct hyperuricemia. Perhaps, in spite of the evidence, clinicians think of gout as an ancient disorder that is no longer prevalent.
The mechanisms responsible for hyperuricemia have been understood for decades. But current breakthroughs are increasing our understanding of these processes.4 With the basic science and epidemiology of gout now sharing the research spotlight, it’s time to revisit the etiology, stages, diagnosis, and treatment of gout and provide an update on therapies in the pipeline.
The etiology of gout
When uric acid in the circulation reaches supersaturation levels (~6.8 mg/dL), urate crystals may form. Urate is the ionized form of uric acid and the end product of purine metabolism. Derived from both dietary and endogenous sources, purines are eliminated by both the kidney and the gut. When uric acid is overproduced or underexcreted, the stage is set for hyperuricemia. In certain conditions (e.g., cool peripheral joints/tissues or damaged/traumatized joints) or with rapid shifts in circulating uric acid, an inflammatory response to these precipitates may occur. A rapid intense inflammatory response can lead to an acute gout flare. Chronic crystal deposition (i.e., sustained over decades) can result in chronic gouty arthritis. Approximately 20% of hyperuricemic patients suffer from gout.8 The higher the uric acid elevation and the longer it lasts, the greater the likelihood of gout.